A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest

Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop an assay detecting the neo-epitope generated by caspase-6 cleavage of GFAP (GFAP-C6), and to assess the ability of GFAP-C6 to reflect pathological processes in patients suffering a cardiac arrest and subsequent global cerebral ischemia. Anti-GFAP-C6 antibodies recognized their specific target sequence, and dilution and spike recoveries in serum were within limits of ±20% reflecting high precision and accuracy of measurements. Intra- and inter-assay CVs were below limits of 10% and 15%, respectively. Serological levels of GFAP-C6 were significantly elevated 72 hours after CA (Mean±SD) (20.39±10.59 ng/mL) compared to time of admission (17.79±10.77 ng/mL, p<0.0001), 24 hours (17.40±7.99 ng/mL, p<0.0001) and 48 hours (17.87±8.56 ng/mL, p<0.0001) after CA, but were not related to neurological outcome at day 180. GFAP-C6 levels at admission, 24, 48, and 72 hours after cardiac arrest correlated with two proteolytic fragments of tau, tau-A (r = 0.30, r = 0.40, r = 0.50, r = 0.53, p < 0.0001) and tau-C (r = 54, r = 0.48, r = 0.55, r = 0.54, p < 0.0001), respectively. GFAP-C6 levels did not correlate with other markers of CNS damage; total tau, NSE and S100B. In conclusion, we developed the first assay detecting a caspase-6 cleaved fragment of GFAP in blood. Increased levels at 72 hours after cardiac arrest as well as moderate correlations between GFAP-C6 and two other blood biomarkers of neurodegeneration suggest the ability of GFAP-C6 to reflect pathological processes of the injured brain. Investigations into the potential of GFAP-C6 in other types of CNS injury are warranted

Osborn waves following out-of-hospital cardiac arrest:Effect of level of temperature management and risk of arrhythmia and death

Background: The Osborn or J-wave, an upright deflection of the J-point on the electrocardiogram (ECG), is often observed during severe hypothermia. A possible relation between Osborn waves (OW) and increased risk of ventricular arrhythmia has been reported. We sought to determine whether the level of targeted temperature management (TTM) following out-of-hospital cardiac arrest (OHCA) affects the prevalence of OW and to assess the associations between OW and risk of ventricular arrhythmia and death. Methods and results: The present study is part of the TTM-trial ECG-substudy (including OHCA-patients randomized to TTM at 33 °C vs. 36 °C from 24 of 36 sites). Serial 12-lead ECGs from 680 (94%) patients were analysed and stratified by OW at predefined time-points (0, 4, 28, 36, 72-h after admission). On admission, the overall prevalence of OW was 16%, increasing to 32% at target temperature, with higher prevalence in the 33 °C-group (40% vs. 23%, p < 0.0001). No difference in prevalence was found between the 33 °C- and 36 °C-groups on admission (18% vs. 14%, p =.11) or after rewarming (13% vs. 10%, p =.44). OW were not associated with increased risk of ventricular arrhythmia (Odds ratio = 0.78 (0.51–1.20), p =.26), but associated with significantly lower 180-day mortality as compared to no OW (38% vs. 52%, plog-rank = 0.001) in univariable analyses only. Conclusion: OW are frequent during TTM, particularly in patients treated with 33 °C. OW are not associated with increased risk of ventricular arrhythmia, and may be considered a benign physiological phenomenon, associated with lower mortality in univariable analyses

Data on association between QRS duration on prehospital ECG and mortality in patients with confirmed STEMI

Data presented in this article relates to the research article entitled âAssociation between QRS duration on prehospital ECG and mortality in patients with suspected STEMIâ (Hansen et al., in press) [1].Data on the prognostic effect of automatically recoded QRS duration on prehospital ECG and presence of classic left and right bundle branch block in 1777 consecutive patients with confirmed ST segment elevation AMI is presented. Multivariable analysis, suggested that QRS duration >111 ms, left bundle branch block and right bundle branch block were independent predictors of 30 days all-cause mortality. For interpretation and discussion of these data, refer to the research article referenced above

MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction - DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy

Background Midregional proadrenomedullin ( MR ‐pro ADM ) has demonstrated prognostic potential after myocardial infarction ( MI ). Yet, the prognostic value of MR ‐pro ADM at admission has not been examined in patients with ST‐segment–elevation MI ( STEMI ). Methods and Results The aim of this substudy, DANAMI‐3 (The Danish Study of Optimal Acute Treatment of Patients with ST ‐segment–elevation myocardial infarction), was to examine the associations of admission concentrations of MR ‐pro ADM with short‐ and long‐term mortality and hospital admission for heart failure in patients with ST ‐segment–elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR ‐pro ADM was 0.64 nmol/L (25th–75th percentiles, 0.53–0.79). Within 30 days 23 patients (2.0%) died and during a 3‐year follow‐up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR ‐pro ADM was, in adjusted models, associated with an increased risk of 30‐day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01–7.11; P =0.049), long‐term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97–5.29; P &lt;0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32–5.58; P =0.007). For 30‐day and 3‐year mortality, the area under the curve for MR ‐pro ADM was 0.77 and 0.78, respectively. For 3‐year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85; P =0.02) after addition of MR ‐pro ADM . Conclusions Elevation of admission MR ‐pro ADM was associated with long‐term mortality and heart failure, whereas the association with short‐term mortality was borderline significant. MR ‐pro ADM may be a marker of prognosis after ST‐segment–elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models. Clinical Trial Registration URL : http:/www.ClinicalTrials.gov /. Unique identifiers: NCT 01435408 and NCT 01960933. </jats:sec

Radiation Testing Campaign for a New Miniaturised Space GPS Receiver

This paper describes the radiation susceptibility testing and analysis of a miniaturised space Global Positioning System (GPS) receiver for small satellite applications. Tests on commercial-off-the-shelf (COTS) parts included total ionising dose (TID), single-event effect (SEE) testing and receiver operational effects under heavy ion exposure.</p

Randomized clinical trials of patients with acute myocardial infarction-related cardiogenic shock: a systematic review of used cardiogenic shock definitions and outcomes

Background: Cardiogenic shock (CS) is a critical complication to acute myocardial infarction (AMI), with short-term mortality rates exceeding 40%. However, no international consensus of a CS definition exists. This may compromise interstudy comparability. Aims: The aim of the current study was to review differences and similarities of CS enrolment criteria in AMI-related CS randomized clinical trials (RCT). Methods: From the electronic databases MEDLINE and EMBASE we identified all AMI-related CS trials.Results: A total of 19 trials comprising a total of 2674 unique patients with CS were identified. Seven trials investigated left ventricular assist devices, eight investigated medical treatments, three percutaneous coronary intervention (PCI), and one trial investigated targeted temperature management. The inclusion criteria, baseline hemodynamics, endpoints, and mortality varied markedly between trials. Hypotension was the most frequent overall inclusion criterion (17 [90%] trials), and a systolic blood pressure &lt;90 mm Hg (and/or need of vasopressors) was the most frequently used limit. Twelve (63%) trials had signs of impaired end-organ perfusion as an inclusion criterion and 10 (53%) signs of impaired cardiovascular function most frequently low cardiac index and reduced left ventricular ejection fraction. Ten (53%) trials included patients resuscitated from a cardiac arrest, three trials excluded cardiac arrest patients whereas six trials did not state whether cardiac arrest was an exclusion criterion. Mortality ranged from 8% to 73%. Conclusions: The RCTs of AMI-related CS have marked heterogeneity in enrolment criteria and outcomes potentially hampering interstudy comparability. The overall consensus of CS enrolment criteria appears needed for future selection of patients